Genetic abnormalities in mammary ductal intraepithelial neoplasia-flat type ("clinging ductal carcinoma in situ"): a simulator of normal mammary epithelium.

摘要: BACKGROUND Mammary ductal intraepithelial neoplasia (DIN)-flat type (“clinging carcinoma in situ [DCIS]”) generally is a subtle epithelial alteration characterized by one or few layer(s) of atypical cells replacing the native epithelium. The “low power” appearance DIN-flat can be misinterpreted easily as “normal” because frequent absence multilayered proliferation and often cytologic atypia. Because it presents an unrecognized lesion association with tubular carcinoma, to authors' knowledge clinical biologic significance this has not been well established. METHODS Using polymerase chain reaction, authors examined DNA extracts from microdissected areas 22 cases extensive “clinging DCIS,” including 13 associated infiltrating 5 more conventional types DCIS. Eight polymorphic markers high rate loss heterozygosity (LOH) classic DCIS were selected identify possible genetic alterations on chromosomes 2p, 3p, 11q, 16q, 17q. Two also used for assessment clonality means X chromosome inactivation (methylation pattern human androgen receptor [HUMARA] gene). RESULTS LOH was detected 17 lesions (77%), monoclonality established 2 analyzed. most common at 11q21-23.2, 16q23.1-24.2, 3p14.2 LOH 50%, 45%, 41%, respectively, informative cases. showed same identified adjacent carcinoma. In contrast type, perfectly normal mammary epithelium very infrequently (1 16 cases; 6%) LOH. CONCLUSIONS The represents earliest, morphologically recognizable, neoplastic breast. Recognition important only early detection intraductal but prevent misinterpretation utilization control studies. This distinctive could crucial explanation least part > 20% reported incidence breast recurrence observed despite ostensibly “negative” margins biopsies. Cancer 2000;88:2072–81. © 2000 American Society.